An aneurysm is an abnormal bulging or ballooning of a blood vessel. Rupture of brain aneurysms can cause stroke, death, or disability. Around at least one-third of people who have a brain aneurysm that ruptures will die within 30 days of the rupture. Of the survivors, around half of the survivors suffer some permanent loss of brain function. Many aneurysms are not identified until they rupture. However, identification of intact aneurysms is increasing due to increased outpatient imaging. Ruptured aneurysms must be treated to stop the bleeding or to prevent re-bleeding. Intact aneurysms may or may not be treated to prevent rupture, depending on their characteristics. Wide neck aneurysms are less prone to rupture, but harder to treat. In the U.S., it has been estimated that over 10 million people have brain aneurysms and 30,000 people each year have a brain aneurysm that ruptures.
Several approaches can be used to treat brain aneurysms. These different approaches can be divided into three categories: (1) approaches involving treatment outside the vessel; (2) approaches involving treatment inside the aneurysm; and (3) approaches involving treatment in the parent vessel. Some of these approaches can be used together. Each of these approaches has some disadvantages, as discussed below.
1. Treatment Outside the Vessel
Clipping: Clipping is the application of a small clip to the aneurysm neck from outside the vessel to seal off the aneurysm. For most brain aneurysms, this involves invasive surgery including removing a section of the skull. Clipping began in the 1930's and is well-established. Clipping is more common in the U.S. than in Europe. Around half of all aneurysms are treated by clipping. However, clipping is decreasing. There are many aneurysm clips. Potential disadvantages of clipping can include: significant health risks associated with major surgery of this type; and long recovery times, even when the surgery itself goes well.
2. Treatment Inside the Aneurysm:
Metal Coils: Metal coiling is the endovascular insertion of metal coils into the aneurysm to reduce blood flow and promote embolization in the aneurysm. Historically, metal coils have been platinum. Coils are more common in Europe than in the U.S. There are many examples of metal coils. Potential disadvantages of metal coils can include: low percentage of aneurysm volume filled—and low occlusion is associated with a higher risk of rupture; compaction of coils over time; risk of recanalization; potential prolapse of coils into the parent vessel; difficulty later clipping aneurysms filled with metal coils, if needed; pressure from the coils on surrounding brain tissue; inability of coils to treat all aneurysms; and expense of metal coils (especially platinum coils).
Combination Metal/Textile/Foam/Gel Coils: Coils with a combination of metal and other materials can be used to try to achieve greater occlusion volume than metal coils alone. These other materials include textile, foam, and gel elements. Textile strands can be woven into the coils to add bulk. Coils can be covered with soft foam. Gel elements can be strung together into elongated structures. Examples of such approaches for embolizing aneurysms include: U.S. Pat. No. 5,382,259 (Phelps et al.), U.S. Pat. No. 5,522,822 (Phelps et al.), U.S. Pat. No. 5,690,666 (Berenstein et al.), U.S. Pat. No. 5,718,711 (Berenstein et al.), U.S. Pat. No. 5,749,894 (Engelson), U.S. Pat. No. 5,976,162 (Doan et al.), U.S. Pat. No. 6,024,754 (Engelson), U.S. Pat. No. 6,299,619 (Greene, Jr. et al.), U.S. Pat. No. 6,602,261 (Greene, Jr. et al.), U.S. Pat. No. 6,723,108 (Jones et al.), U.S. Pat. No. 6,979,344 (Jones et al.), U.S. Pat. No. 7,070,609 (West), and U.S. Pat. No. 7,491,214 (Greene, Jr. et al.), and U.S. Patent Applications 20040158282 (Jones, Donald et al.), 20050267510 (Razack, Nasser), and 20060058834 (Do, Hiep et al.). Potential disadvantages of combination coils can include: remaining gaps between loops; compaction of coils over time; risk of recanalization; potential prolapse of coils into the parent vessel; difficulty clipping aneurysms filled with coils with metal components later if needed; pressure from the coils on surrounding brain tissue; inability of coils to treat all aneurysms; and expense of metal coils.
Inflatable Balloons: Approximately two decades ago, there were numerous efforts to treat aneurysms by permanently filling them with inflatable balloons. These efforts were largely abandoned due to the risks of balloon deflation, prolapse into the parent vessel, aneurysm rupture, and recanalization. There are, however, examples of relatively recent art using inflatable balloons to treat aneurysms: U.S. Pat. No. 6,569,190 (Whalen et al.) and U.S. Pat. No. 7,083,643 (Whalen et al.), and U.S. Patent Applications 20030135264 (Whalen et al.), 20030187473 (Berenstein, Alejandro et al.), 20060292206 (Kim, Steven et al.), 20070050008 (Kim, Steven et al.), and 20070055355 (Kim, Steven et al.). Potential disadvantages of using inflatable balloons to permanently fill aneurysms can include: balloon deflation; prolapse of the balloon into the parent vessel; aneurysm rupture due to balloon pressure; and recanalization.
Manually-Activated Mesh Occluders: Another approach to treating aneurysms involves inserting into the aneurysm a mesh structure, generally metal, that can be expanded or contracted by human-controlled mechanical motion so as to block the aneurysm neck and/or to fill the main volume of the aneurysm. For example, a wire structure can be inserted through the aneurysm neck in a narrow configuration and then transformed into an “hour-glass” shape that collapses to block the aneurysm neck when activated by a human controller. Examples of metal structures that occlude the aneurysm by manually-activated expansion or contraction include: U.S. Pat. No. 5,928,260 (Chin et al.), U.S. Pat. No. 6,344,048 (Chin et al.), U.S. Pat. No. 6,375,668 (Gifford et al.), U.S. Pat. No. 6,454,780 (Wallace), U.S. Pat. No. 6,746,468 (Sepetka et al.), U.S. Pat. No. 6,780,196 (Chin et al.), and U.S. Pat. No. 7,229,461 (Chin et al.), and U.S. Patent Applications 20020042628 (Chin, Yem et al.), 20020169473 (Sepetka, Ivan et al.), 20030083676 (Wallace, Michael), 20030181927 (Wallace, Michael), 20040181253 (Sepetka, Ivan et al.), 20050021077 (Chin, Yem et al.), 20060155323 (Porter, Stephen et al.), 20070088387 (Eskridge, Joseph et al.), 20070106311 (Wallace, Michael et al.), and 20080147100 (Wallace, Michael). Potential disadvantages of such manually-activated metal occluders include: difficulty engaging the necks of wide-neck aneurysms; difficulty filling irregularly-shaped aneurysms with standard-shaped mesh structures; risk of rupture when pinching the aneurysm neck or pushing on the aneurysm walls; and protrusion of the proximal portion of “hour-glass” designs into the parent vessel.
Self-Expanding Standard-Shape Occluders: Another approach to treat aneurysms uses standard-shaped structures that self-expand when released into the aneurysm. For example, the structure may be a mesh of “shape memory” metal that automatically expands to a standard shape when released from the confines of the catheter walls. As another example, the structure may be a gel that expands to a standard shape when exposed to moisture. Examples of such self-expanding structures include: U.S. Pat. No. 5,766,219 (Horton), U.S. Pat. No. 5,916,235 (Guglielmi), U.S. Pat. No. 5,941,249 (Maynard), U.S. Pat. No. 6,409,749 (Maynard), U.S. Pat. No. 6,506,204 (Mazzocchi), U.S. Pat. No. 6,605,111 (Bose et al.), U.S. Pat. No. 6,613,074 (Mitelberg et al.), U.S. Pat. No. 6,802,851 (Jones et al.), U.S. Pat. No. 6,811,560 (Jones et al.), U.S. Pat. No. 6,855,153 (Saadat), U.S. Pat. No. 7,083,632 (Avellanet et al.), U.S. Pat. No. 7,306,622 (Jones et al.), and U.S. Pat. No. 7,491,214 (Greene, Jr. et al.), and U.S. Patent Applications 20030093097 (Avellanet, Ernesto et al.), 20030195553 (Wallace, Michael et al.), 20050033349 (Jones, Donald et al.), 20060052816 (Bates, Brian et al.), and 20060235464 (Avellanet, Ernesto et al.) and WIPO Patents WO/2006/084077 (Porter, Stephen et al.) and WO/1996/018343 (McGurk et. al.). Potential disadvantages of such self-expanding standard-shape structures can include: risk of prolapse into the parent vessel, especially for wide-neck aneurysms; difficulty occluding irregularly-shaped aneurysms with standard shape structures and associated risk of recanalization; and difficulty generating the proper amount of force (not too much or too little) when engaging the aneurysm walls with a standard-shaped self-expanding structure.
Self-Expanding Custom-Modeled Occluders: A variation on self-expanding standard-shape occluders (discussed above) are self-expanding occluders that are custom modeled before insertion so as to fit the shape of a particular aneurysm. As an example sequence—the aneurysm can be imaged, the image is used to custom model the occluding structure, the occluding structure is compressed into a catheter, the occluding structure is inserted into the aneurysm, and the occluding structure then self-expands to fill the aneurysm. The occluding structure may be made from a gel that expands upon contact with moisture. Examples in the related art involving self-expanding custom-modeled occluding structures include: U.S. Pat. No. 5,766,219 (Horton), U.S. Pat. No. 6,165,193 (Greene, Jr. et al.), U.S. Pat. No. 6,500,190 (Greene, Jr. et al.), U.S. Pat. No. 7,029,487 (Greene, Jr. et al.), and U.S. Pat. No. 7,201,762 (Greene, Jr. et al.), and U.S. Patent Application 20060276831 (Porter, Stephen et al.). Potential disadvantages of self-expanding custom-modeled occluders can include: the complexity and expense of imaging and modeling irregularly-shaped aneurysms; difficulty compressing larger-size structures into a catheter; difficulty inserting the occluding structure in precisely the correct position; and difficulty getting a gelatinous surface to anchor solidly to aneurysm walls.
Congealing Liquid or Gel: Another approach to treating aneurysms involves filling the aneurysm with a liquid or gel that congeals rapidly. Examples of this approach include the following: U.S. Pat. No. 6,569,190 (Whalen et al.), U.S. Pat. No. 6,626,928 (Raymond et al.), U.S. Pat. No. 6,958,061 (Truckai et al.), and U.S. Pat. No. 7,083,643 (Whalen et al.), and U.S. Patent Application 20030135264 (Whalen et al.). Potential disadvantages of a congealing liquid or gel can include: leakage of the congealing substance into the parent vessel, potentially causing a stroke; difficulty filling the entire aneurysm if the substance begins to congeal before the aneurysm is full; and seepage of toxic substances into the blood stream.
Biological or Pharmaceutical Agents: Biological and/or pharmaceutical agents can enhance the performance of a variety of mechanical treatment methods for aneurysms. For example, they can speed up the natural embolization process to occlude the aneurysm. Some examples of using biological and/or pharmaceutical agents to treat aneurysms include: U.S. Patent Applications 20060206139 (Tekulve, Kurt J.), 20070168011 (LaDuca, Robert et al.), and 20080033341 (Grad, Ygael). Currently, biological and/or pharmaceutical approaches are not sufficient as stand alone treatment approaches for many cases. Accordingly, they share most of the potential disadvantages of the baseline approach to which the biological or pharmaceutical agents are added.
Embolic-Emitting Expanding Members: Another approach involves an expanding member within the aneurysm that emits embolic elements into the aneurysm. Examples of such expanding members include bags, meshes, and nets. Examples of embolic elements include coils and congealing liquids. This can be viewed as another way to block the aneurysm neck while delivering embolics into the volume of the aneurysm. For example, the distal portion of an expanding bag may leak embolic elements into the aneurysm, but the proximal portion of the expanding member does not leak embolics into the parent vessel. Examples of this approach include: U.S. Pat. No. 6,547,804 (Porter et al.) and U.S. Patent Applications 20040098027 (Teoh, Clifford et al.), 20060079923 (Chhabra, Manik et al.), and 20080033480 (Hardert, Michael). Potential disadvantages are as follows. Since the expanding member “leaks,” it may have insufficient expansion force to adequately anchor against the aneurysm walls or to seal off the aneurysm neck. As a result of poor anchoring, the bag may prolapse into the parent vessel. Also, as a result of poor sealing of the aneurysm neck, embolics may leak into the parent vessel.
Shape Memory Structures inside Expanding Members: A variation on the shape memory approach above involves the addition of an expanding member around the shape memory structure. Examples of this approach include: U.S. Pat. No. 5,861,003 (Latson et al.), U.S. Pat. No. 6,346,117 (Greenhalgh), U.S. Pat. No. 6,350,270 (Roue), U.S. Pat. No. 6,391,037 (Greenhalgh), and U.S. Pat. No. 6,855,153 (Saadat). The potential disadvantages of this approach are similar to those for uncovered shape memory occluders: risk of prolapse into the parent vessel, especially for wide-neck aneurysms; difficulty occluding irregularly-shaped aneurysms with standard shape structures and associated risk of recanalization; and difficulty generating the proper amount of force (not too much or too little) when engaging the aneurysm walls with a standard-shaped self-expanding structure.
Accumulating Coils inside Expanding Members: A variation on the standard coiling approach above involves the addition of an expanding member around the accumulating coils. Examples of this approach include: U.S. Pat. No. 5,334,210 (Gianturco), U.S. Pat. No. 6,585,748 (Jeffree), and U.S. Pat. No. 7,153,323 (Teoh et al.), and U.S. Patent Applications 20060116709 (Sepetka, Ivan et al.), 20060116712 (Sepetka, Ivan et al.), and 20060116713 (Sepetka, Ivan et al.). Potential disadvantages of this approach are similar to those for coils alone, including: compaction of coils over time; risk of recanalization due to “bumpy” coil-filled expanding member; difficulty clipping aneurysms filled with metal coils later if needed; pressure from the coils on surrounding brain tissue; inability to treat all aneurysms; and expense of metal coils (especially platinum coils).
3. Treatment in the Parent Vessel:
Standard (High-Porosity) Stent: A stent is a structure that is inserted into a vessel in a collapsed form and then expanded into contact with the vessel walls. Standard stents are generally highly porous, metal, and cylindrical. A high-porosity stent allows blood to flow through the stent walls if there are any branching vessels or other openings in the vessel walls. Blood flow through a stent wall into a branching vessel is desirable; blood flow through a stent wall into an aneurysm is not. Accordingly, a high-porosity stent in the parent vessel is not a good stand-alone aneurysm treatment. A high-porosity in the parent vessel can, however, help to keep coils or other embolic members from escaping out of the aneurysm into the parent vessel. Examples of this approach include: U.S. Pat. No. 6,096,034 (Kupiecki et al.), U.S. Pat. No. 6,168,592 (Kupiecki et al.), U.S. Pat. No. 6,344,041 (Kupiecki et al.), U.S. Pat. No. 7,211,109 (Thompson), and U.S. Pat. No. 7,303,571 (Makower et al.), and U.S. Patent Application 20080045996 (Makower, Joshua et al.). Potential disadvantages of this approach can include many of the problems associated with use of the embolic members alone. For example, using a high-porosity stent in the parent vessel in combination with coils in the aneurysm still leaves the following disadvantages of using coils alone: low percentage of aneurysm volume filled (and low occlusion is associated with a higher risk of rupture); compaction of coils over time; significant risk of recanalization; difficulty clipping aneurysms filled with metal coils later if needed; pressure from the coils on surrounding brain tissue; inability of coils to treat all aneurysms; and expense of metal coils (especially platinum coils).
Uniformly Low-Porosity Stent: Another approach involves inserting a uniformly low-porosity stent into the parent vessel. The low-porosity stent blocks the flow of blood through the stent walls into the aneurysm, causing beneficial embolization of the aneurysm. For example, the stent may have one or more layers that are impermeable to the flow of liquid. Unlike a standard (high-porosity) stent, this approach can be used as a stand-alone aneurysm treatment. Examples of this approach include: U.S. Pat. No. 5,645,559 (Hachtman et al.), U.S. Pat. No. 6,270,523 (Herweck et al.), U.S. Pat. No. 6,331,191 (Chobotov), U.S. Pat. No. 6,342,068 (Thompson), U.S. Pat. No. 6,428,558 (Jones et al.), U.S. Pat. No. 6,656,214 (Fogarty et al.), U.S. Pat. No. 6,673,103 (Golds et al.), U.S. Pat. No. 6,786,920 (Shannon et al.), and U.S. Pat. No. 6,790,225 (Shannon et al.), and U.S. Patent Application 20080319521 (Norris, Stephanie et al.). Potential disadvantages of this approach can include: undesirably blocking blood flow to branching vessels that are close to the aneurysm and are covered by the stent wall; and difficulty achieving a snug fit across the neck of the aneurysm if the parent vessel is curved, twisted, or forked.
Uniformly Intermediate-Porosity Metal Stent: This approach pursues creation of a stent with a uniform intermediate porosity that provides a compromise between the benefits of a high-porosity stent in the parent vessel (good blood flow to nearby branching vessels) and the benefits of a low-porosity stents in the parent vessel (blocking blood flow to the aneurysm). Examples of this approach include: U.S. Pat. No. 5,769,884 (Solovay) and U.S. Pat. No. 7,306,624 (Yodfat et al.) and U.S. Patent Applications 20070219619 (Dieck, Martin et al.), 20070239261 (Bose, Arani et al.), and 20080039933 (Yodfat, Ofer et al.). The main potential disadvantage of this approach is that it may do neither function well. It may unreasonably block flow to a branching vessel (causing a stroke) and inadequately block blood flow to the aneurysm (leaving it vulnerable to rupture).
Pre-Formed Differential Porosity Stent: This approach involves creates a stent with different levels of porosity for different wall areas, before the stent is inserted into the parent vessel. The goal is to place wall areas with high porosity over openings to branching vessels and to place wall areas with low porosity over the neck of the aneurysm. Examples of this approach include: U.S. Pat. No. 5,723,004 (Dereume et al.), U.S. Pat. No. 5,948,018 (Dereume et al.), U.S. Pat. No. 5,951,599 (McCrory), U.S. Pat. No. 6,063,111 (Hieshima et al.), U.S. Pat. No. 6,165,212 (Dereume et al.), U.S. Pat. No. 6,309,367 (Boock), U.S. Pat. No. 6,309,413 (Dereume et al.), U.S. Pat. No. 6,770,087 (Layne et al.), U.S. Pat. No. 7,052,513 (Thompson), and U.S. Pat. No. 7,186,263 (Golds et al.), and U.S. Patent Applications 20070207186 (Scanlon, John et al.), 20070219610 (Israel, Henry M.), 20070239261 (Bose, Arani et al.), 20070276469 (Tenne, Dirk), 20070276470 (Tenne, Dirk), and 20080004653 (Sherman, Darren et al.). Potential disadvantages of this approach can include: difficultly and expense involved in matching a specific anatomic configuration (curvature, branching, neck size, etc) with a set of preformed stents; and difficulty of precise placement of the stent to properly align the porous and non-porous areas with branching vessels and the aneurysm, respectively.
Post-Implantation Filling Between Stent Wall and Vessel Wall: Unlike the previous approach involving a stent with differential porosity across different wall areas before implantation, this approach creates differential porosity across different wall areas after the stent is implanted. In particular, this approach involves filling the gap between the stent wall and the vessel wall with an embolizing substance such as a congealing liquid or gel. Examples of this approach include: U.S. Pat. No. 5,769,882 (Fogarty et al.), U.S. Pat. No. 5,951,599 (McCrory), and U.S. Pat. No. 6,096,034 (Kupiecki et al.), and U.S. Patent Application 20070150041 (Evans, Michael et al.). Potential disadvantages of this approach can include: difficulty injecting the embolizing substance through the stent wall without having it leak back into the parent vessel; potential leakage of embolizing substance into branching vessels; challenges containing the embolic material within curving vessels or vessels with irregular walls; and difficulty of use to fill narrow-neck aneurysms.
Post-Implantation Surface Modification: This approach creates differential porosity across different wall areas after stent implantation by targeted surface modification using chemicals or targeted energy. For example, exposure of the portion of the stent wall covering the aneurysm neck to certain chemicals or energy may cause that porosity of the wall to decrease. An example of this approach is U.S. Pat. No. 7,156,871 (Jones et al.). Potential disadvantages of this approach can include: difficulty getting a good seal between the stent wall and aneurysm neck in curved, twisted, or branching vessels; and negative effects of chemicals or targeted energy on surrounding vessel or brain tissue.
In sum, although there has been significant progress in developing options for treating brain aneurysms, there are still high rates of death and disability and still disadvantages to the treatment options available.